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Transcript
Chapter 9: Persistent
Depressive Disorder
(PPD)
Daniel N. Klein
Sarah R. Black
Background
 Depressive disorders traditionally conceptualized as
episodic, remitting conditions
 Shift to viewing depression as recurrent and chronic
 Reality is variability in course (e.g., single episode, recurrent
episodes with full remission in between, chronic depression)
 Chronic depressions ~30% of cases in community and
~50% in outpatient settings
 Evidence that chronicity is a key aspect of the clinical and
etiological heterogeneity of depression that should be
considered in both clinical practice and research
Description and
Diagnostic Criteria
DSM-5 Criteria:
Dysthymic Disorder
 Chronic course, persistent symptoms, insidious onset
 At least two of six depressive symptoms required:
 Low energy or fatigue, insomnia or hypersomnia, poor appetite or
overeating, low self-esteem, poor concentration or difficulty making
decisions, and feelings of hopelessness
 Cognitive, affective, social-motivational symptoms more
common than vegetative symptoms
 At some point, most individuals experience superimposed
MDEs (“double depression”)
 With DSM-IV, given given both MDD and dysthymia diagnoses
if experience double depression
Persistent Depressive Disorder
(PDD)
 Chronic course: most of day, more days than not, for at least
two years
 Persistent symptoms: no symptom-free periods of more than 2
months
 Insidious onset typical: but ok if MDD present during first 2
years
 At least 2 of 6 depressive symptoms required:
 Low energy or fatigue, insomnia or hypersomnia, poor appetite or
overeating, low self-esteem, poor concentration or difficulty making
decisions, and feelings of hopelessness
 Cognitive, affective, social-motivational symptoms more common in PDD than
are vegetative symptoms
 At some point, most individuals experience superimposed MDEs
( called “double depression” in the past)
 In DSM-5, those who would meet for DSM-IV chronic MDD will now receive PDD
diagnosis
Summary of DSM-5 Changes for
Depressive Disorders
 Persistent Depressive Disorder – consolidation of DSM-
IV criteria for chronic MDD & dysthymic disorder
 Same as criteria for dysthymia in DSM-IV, except D criteria
 DSM-IV: No MDE has been present during first 2 years of the
disturbance
 DSM-5: Criteria for a MDD may be continuously present for first 2
years
DSM-5 Persistent Depressive
Disorder: Specifiers
 Partial remission versus full remission
 Early Onset (before 21) versus Late
 With pure dysthymic syndrome (no MDD in last 2
years)
 With persistent MDD (MDD met continuously in last 2
years- used to be called chronic depression)
 MILD: just meeting criteria and impairment is minor
 MODERATE: between mild and severe
 SEVERE: many criteria met, marked impairment and
serious distress
Chronic Versus Nonchronic
Depressions
 Support for dysthymia versus MDD distinction:
 Milder symptoms, but dysthymia more severe on almost all
other variables (e.g., greater suicidality and comorbidity, lower selfesteem)
 Validity of chronic–nonchronic MDD distinction less clear:
 However, some meaningful differences (e.g., chronic has earlier
onset, poorer work and social functioning)
 Support for broader chronic-nonchronic distinction:
 Meaningful differences (e.g., chronic associated with greater childhood
adversity, earlier age of onset)
 Chronic depression aggregates specifically in families
 Distinction relatively stable over time
Forms of Chronic Depression
 Virtually no differences found between different forms of
chronic depression (on variables like: comorbidity, personality, familial
psychopathology, course, outcome)
 Thus, distinctions among various forms of chronic depression
do not appear to be meaningful, in contrast to chronic–
nonchronic distinction
 Decision made to combine different forms of chronic
depression into single category in DSM-IV
Dysthymia versus Depressive
Personality Disorder
 Equivalent constructs in DSM-III
 Depressive PD was a provisional diagnosis in need of
further study of DSM-IV; it was defined in terms of traits
(mostly cognitive) and did not require persistent
depressed mood
 Decision made not to include it in DSM-5 though it does
appear to lie within the spectrum of chronic epressive
disorders and does not require persistent depressed
mood
Subtypes of Dysthymia
 Several distinct etiological pathways
 Early (< 21) & late (≥ 21) onset specifiers in DSM-IV
 Early: Higher familial loading, childhood adversity, and so on
 Late: Greater association with stressful life events
 Subtypes within early-onset proposed:
 Subaffective vs. character spectrum
 Strong familial liability vs. early adversity and increased
sensitivity of behavioral and neurobiological stress response
systems
DSM-5 Changes
 Now “Persistent Depressive Disorder”: Consolidation of
DSM-IV criteria for chronic MDD and dysthymic disorder
 Same as criteria for dysthymia in DSM-IV, except D criteria
 DSM-IV: “No MDE has been present during first 2 years of the
disturbance”
 DSM-5: “Criteria for a MDD may be continuously present for 2 years”
Epidemiology
Prevalence and Comorbidity
 Dysthymia: 12 months 0.5%-2.5%; lifetime 0.9%-6.4%
 Chronic MDD: 12 months 1.5%; lifetime, 3.1%
 Chronic depression combined: Lifetime 4.6%
 Prevalence of dysthymia and chronic MDD almost 2x
greater in women than men
 Higher in developed countries and among individuals with
lower incomes
 High comorbidity with anxiety, substance use, and
personality disorders (especially avoidant, borderline, dependent PDs)
Impairment
 Severity and chronicity contribute additively to functional
impairment in depression
 Thus, dysthymia associated with equal or greater impairment
than nonchronic MDD
 Double depression greater impairment than either alone
 Impairment in many areas (e.g., work functioning and marital, family,
and social relationships)
 Significant impairment seen even after recovery
Course and Prognosis
Course and Prognosis
 In a 10-year follow-up study of dysthymia and
double depression…
 74% recovery rate
 52 month median time to recovery
 71% relapsed after recovery
 6% developed manic or hypomanic episodes
 84% superimposed MDEs
 Predictors of greater depressive symptoms at 10 years:
Greater familial loading, history of poor maternal relationship, childhood
sexual abuse
 Comorbid PD predicted slower rate of improvement
Chronic Depression in
Youth and Elderly
Dysthymia in Children and
Adolescents
 DSM-5: Minimum 1-year duration (versus 2 for adults);
can have irritable instead of depressed mood
 Children: 0.1% point prevalence
 Adolescents: 0.5% prevalence; 3% lifetime
 High comorbidity with anxiety and disruptive behavior
disorders
 Course
 Most eventually have superimposed MDEs
 Almost all eventually recover; median episode duration 4 years
 Greater risk of developing bipolar
Dysthymia and Older Adults (> 65)
 Prevalence: 2%–6%
 Most late-onset (> 21)
 Compared to nonelderly with dysthymia: Lower rates of Axis I and
II comorbidity, higher rates of recent life events, more GMCs
 Recovery rate: 12%–38% (15 months—6 years)
 Predictors of poorer course: Greater symptom severity, social
isolation and low social support, poor self-reported health
Psychosocial Factors
Early Maltreatment and Adversity
 Predict poorer course and outcome
 Link between adversity and chronic depression could be
explained by:
 Comorbidity with other mental disorders; however,
relationship remains after controlling for other disorders
 Third variable (e.g., genes related to both)
 Future directions:
 Establish causal relationship
 Etiological pathways (e.g., development of depressogenic cognitive
schemas)
 Most maltreated children do not later develop chronic
depression; need to look for moderators of association
Personality/Temperament and
Chronic Stress
 Low positive emotionality (PE) and high negative
emotionality (NE) predict poorer course and outcome in
chronic depression
 Also may predict development of chronic depression
 Higher NE and lower PE in chronic than nonchronic
depression and this personality seen after recovery as
well as prior to illness
 Higher levels of chronic stress & daily hassles in chronic
than nonchronic depression
 Chronic stress appears to play causal role in onset or
maintenance of chronic depression (not reverse)
 Reduction or neutralization of ongoing difficulties and “freshstart” events associated with recovery
Cognitive and Interpersonal
Factors
 Similar cognitive factors seen as in nonchronic depression
(e.g., stable and global attributions for negative events, ruminative response
style)
 Directionality of relationship between maladaptive cognitive
processes and depression unclear
 Interpersonal difficulties maintain and prolong depressive
episodes
 Self-propagating processes proposed to maintain depression
(e.g., negative feedback-seeking, excessive reassurance-seeking)
 Predict development of chronic depression
• Greater difficulties after recovery than nonchronic MDD and HCs
• Directionality unclear
Genetic and
Neurobiological
Factors
Familial Aggregation/Genetics
 Evidence of specificity of familial transmission in chronic
depression
 Also higher rates of nonchronic MDD in relatives of probands
with chronic than nonchronic depression
 Several findings suggest chronic depression characterized
by a specific set of interacting genetic and environmental
processes
 Childhood maltreatment moderates association between
5-HTTLR and chronic depression
Neurobiology
 In major mood disorders, evidence of neuroendocrinology,
sleep electrophysiology, and structural and functional brain
abnormalities
 In chronic depression:
 Similar HPA axis abnormalities
 Inconsistent findings for sleep electrophysiology abnormalities
 Similar structural and functional abnormalities
 Too few studies to determine whether differences between
chronic and nonchronic depression (e.g., whether any abnormalities
are greater in or specific to chronic depression)
Assessment
Assessment: Overview
 Challenging task!
 Usually psychological assessments focus on acute conditions
 Dysphoria is “normal” for these individuals, often seek
treatment for superimposed MDE
 Requires careful history of current and past course of
depression
Assessment: Tools
 Structured diagnostic interviews (e.g., SCID):
 Generally only assess for current dysthymia
 Limited information on onset, course, interepisode
symptomatology
 Often miss double depression
 Rating scales (e.g., HAM-D) and self-reports:
 Course not adequately assessed to diagnose chronic




depression
Do not include the most common symptoms of dysthymia
Refer to differences from “normal” or “usual” state
Cornell Dysthymia Rating Scale addresses these problems
General Behavior Inventory (GBI) is the only self-report
measure explicitly developed for chronic mood disorders
Treatment
Treatment: Overview
 Pharmacotherapy
 All antidepressants equally more efficacious than placebo
 Lower placebo response in chronic than nonchronic MDD
 Antidepressants alone appear more efficacious than
psychotherapy alone
 Indirect evidence that different approaches required
 Longer duration of psychotherapy
 More likely to benefit from combined meds and therapy
 Few predictors of differential response
(to different meds or
pharmacotherapy vs. psychotherapy)
 CBASP higher remission for chronically depressed with
childhood adversity, whereas meds superior for individuals
without childhood adversity
 Treatment preference impacts outcomes
Treatment: Psychotherapy
 More efficacious than control conditions, but small effect size
 Minimum 18 sessions for optimal effects
 Cognitive behavioral analysis system of psychotherapy
(CBASP)
 Specifically designed for chronic depression
 Uses behavioral and cognitive techniques to help patients develop
better interpersonal problem-solving skills
 Interpersonal therapy (IPT)
 Psychodynamically inspired therapy that focuses on current
interpersonal problems
 One of few comparisons of CBASP and IPT found higher
remission rate for CBASP at post, but similar effects at 1-year
follow-up
Treatment: Nonresponse,
Continuation and Maintenance
 Nonresponse and partial remission to initial trial of
treatment high among chronically depressed
 Can change medications or
 Switch to/add psychotherapy or pharmacotherapy
 Continuation and maintenance treatment
 Important consideration due to high risk of relapse and
recurrence
 Antidepressants lower risk of relapse and recurrence
compared to placebo
 Some evidence psychotherapy effective as maintenance
treatment
Summary and Future
Directions
Summary
 The various forms of chronic depression appear to be more
alike than different, and may represent variants or different
phases of the same underlying disorder
 Chronic–nonchronic distinction appears to be
meaningful
 Still, some heterogeneity within chronic depression
 Age of onset
 Episodes can last for many years, but most patients
eventually recover
 Risk of recurrence high
 Predictors of poorer course and outcome: Family history, childhood
adversity, comorbid anxiety and PDs, chronic stress
Summary
 Treatment challenges: Entrenched psychopathology,
comorbidity, longstanding interpersonal deficits, chronic
helplessness and hopelessness, depression becoming
integrated into individual’s self-image and daily routine
 Antidepressants and some psychotherapies (e.g., CBASP)
found effective, and combination may be more effective
 Maintenance treatment can prevent recurrences
Future Directions
 Genetically informative studies (e.g., genome-wide association
studies, gene-by-environment interactions)
 Causal processes producing high psychiatric comorbidity
 Etiological pathways
 Protective factors, environmental variables that facilitate
recovery (e.g., “fresh-start” events)
 Developing tools that better assess course
 Psychotherapy: Identifying active ingredients, optimal
parameters, specificity and range of effective treatments
 Improve remission rates from meds and therapy
 How to sequence and combine treatments to optimize
outcomes